The goals of Dr. Eugene Shapiro are: 1) to conduct high quality patient-oriented research to answer important clinical questions and 2) to mentor young physicians who conduct patient-oriented research to help them become successful independent investigators. During the period of the currently-funded K-24 award, Dr. Shapiro has published papers that have had an impact on public health policy and he has mentored a substantial number of trainees and junior members of the faculty who are conducting patient-oriented research projects. Dr. Shapiro's research has focused on the effectiveness of vaccines as they are used in clinical practice and on the clinical epidemiology and outcomes of patients with Lyme disease. He has also been a leader in developing methods to minimize and to assess possible effects of bias in these non- experimental studies. He is conducting an on-going, population-based case-control study of the effectiveness of varicella vaccine over time, a critical public health issue. Dr. Shapiro plans to conduct additional case-control studies of vaccines during the period of this proposal, including an assessment of the effectiveness of influenza vaccine in preventing hospitalization in young children. He also plans to expand into new areas that include infections with emerging respiratory viruses, including human metapneumovirus and a recently identified coronavirus. In addition to defining the clinical epidemiology of these infections, he plans to work with collaborators to assess both clinical and virologic risk factors that may affect the severity of these illnesses. In addition, he will work on a randomized clinical trial of a "wait-and-see" approach to treating otitis media as a strategy to decrease unnecessary use of antibiotics. Dr. Shapiro will serve as a primary mentor for 1-2 new fellows (or young faculty members) each year, in addition to contributing to mentoring many other trainees. If this proposal is funded, it will allow Dr. Shapiro to continue to spend at least 70% of his time serving as a mentor to young investigators and conducting patient-oriented research.